MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma.

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus programmed cell death protein-1 (PD-1) for unresectable hepatocellular carcinoma (HCC) have rarely been evaluated and it is unknown which factors are related to efficacy. AIM: To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC. METHODS: This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022. Overall survival (OS) and progression-free survival (PFS) were determined. The objective response rate (ORR) and disease control rate (DCR) were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors. Additionally, the prognostic factors affecting the clinical outcome were assessed. RESULTS: One hundred and two patients were enrolled with a median follow-up duration of 12.63 months. The median OS was 26.43 months (95%CI: 17.00-35.87), and the median PFS was 10.07 months (95%CI: 8.50-11.65). The ORR and DCR were 61.76% and 81.37%, respectively. The patients with Barcelona Clinic Liver Cancer Classification (BCLC) B stage, early neutrophil-to-lymphocyte ratio (NLR) response (decrease), or early alpha-fetoprotein (AFP) response (decrease > 20%) had superior OS and PFS than their counterparts. CONCLUSION: This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC. The patients with BCLC B-stage disease with early NLR response (decrease) and early AFP response (decrease > 20%) may achieve better clinical outcomes with this triple therapy.

Preventive and Therapeutic Benefits of Natural Ingredients in Photo-Induced Epidermal Dysfunction.

BACKGROUND: The skin, particularly the epidermis, is subjected to various external stresses, including ultraviolet [UV] irradiation. UV irradiation, mainly UVB at wavelength of 280-315 nm, can alter several epidermal functions, including cutaneous inflammation, epidermal hyperproliferation, DNA damage, disruption of epidermal permeability barrier and reduction in stratum corneum hydration levels. Because of the negative impacts of UVB irradiation on epidermal functions, great efforts have been made to develop regimens for the protection of alterations in epidermal function induced by UV irradiation. SUMMARY: While sunscreen can provide physical barrier to UV light, some natural ingredients can also effectively protect the skin from UVB irradiation-induced damages. Studies have demonstrated that either topical or oral administrations of some natural ingredients attenuate UVB irradiation-induced alterations in the epidermal function. The underlying mechanisms by which natural ingredients improve epidermal functions are attributable to antioxidation, stimulation of keratinocyte differentiation, increases in the content of epidermal natural moisturizers and inhibition of inflammation. KEY MESSAGE: Some natural ingredients exhibit protective and therapeutical benefits in photo-induced epidermal dysfunctions via divergent mechanisms.

Partial splenic embolization with embosphere microspheres (700-900 µm) for the treatment of hypersplenism: comparison of selective superior splenic artery embolization and inferior splenic artery embolization.

Objective: To compare clinical outcomes of superior versus inferior splenic artery embolization in partial splenic embolization (PSE) and identify predictors of major complications. Material and methods: This retrospective case-control study included 73 patients who underwent PSE between May 2005 and April 2021. They were divided into two groups: the superior and middle splenic artery embolization group (Group A, n = 37) and the inferior and middle splenic artery embolization group (Group B, n = 36). Outcome differences and major complications between the groups were assessed. Logistic regression was used to analyze potential predictors of major complications, and the optimal cutoff value for splenic embolization rates was determined using the Youden index. Results: There were no significant differences in laboratory and radiological outcomes between the two groups. Group A had a significantly lower incidence of major complications than Group B (p = 0.049), a lower Visual Analog Scale (VAS) score for pain (p = 0.036), and a shorter hospital stay (p = 0.022). Independent risk factors for major complications included inferior and middle splenic artery embolization (odds ratio [OR] = 3.672; 95% confidence interval [CI] = 1.028-13.120; p = 0.045) and a higher spleen embolization rate (OR = 1.108; 95% CI = 1.003-1.224; p = 0.044). The optimal cutoff for spleen embolization rate to predict major complications was 59.93% (sensitivity 77.8%, specificity 63.6%). Conclusion: Using 500-700 µm microspheres for PSE, targeting the middle and superior splenic artery yields similar effects to targeting the middle and inferior artery, but results in lower rates of major complications and shorter hospital stays. To effectively minimize the risk of major complications, the embolization rate should be kept below 59.93%, regardless of the target vessel.

Five New Species of Gymnopilus from Xizang Autonomous Region of China and Surrounding Areas.

The species of Gymnopilus (Hymenogastraceae, Agricales) are commonly recognized as wood-decaying fungi. Certain members of this genus have been identified as psilocybin-producing mushrooms. Gymnopilus exhibits a diverse range and has a global distribution. In this study, a total of seventy-eight specimens were gathered from ten provinces in China. A comprehensive molecular phylogenetic analysis was conducted, employing gene sequences including ITS, nrLSU, nrSSU, rpb1, rpb2, and tef1-α. Additionally, morphological examinations were also carried out. The phylogenetic topology of Gymnopilus from this study generally agreed with previous studies and facilitated the identification of all those specimens. As a result, eleven species, including five newly discovered ones named Gy. gyirongensis, Gy. variisporus, Gy. tomentosiceps, Gy. tenuibasidialis, and Gy. aurantipileatus, were recognized. Significantly, four of the five newly identified species are native to the Xizang Autonomous Region, emphasizing their specialization in this distinctive habitat. This research contributes to our comprehension of Gymnopilus diversity and lays the groundwork for the conservation and sustainable utilization of Gymnopilus resources.

Transcatheter arterial embolization with N-butyl cyanoacrylate for postoperative hemorrhage treatment following pancreatoduodenectomy.

PURPOSE: Postoperative hemorrhage (PPH) is a severe complication of pancreatoduodenectomy (PD) with a mortality rate of 5-20.2% and mortality due to hemorrhage of 11-58%. Transcatheter arterial embolization (TAE) has been widely recommended for PPH, however, TAE with N-butyl cyanoacrylate (NBCA) for PPH treatment has been reported rarely. Therefore, this study aimed to evaluate the safety and efficacy of TAE with NBCA for PPH treatment following PD. METHODS: This retrospective study included 14 male patients (mean age, 60.93 ± 10.97 years) with postoperative hemorrhage following PD treated with TAE using NBCA as the main embolic agent from October 2019 to February 2022. The clinical data, technical and success rate, and complications were analyzed. RESULTS: Among the 14 patients who underwent TAE, the technical and clinical success rates were 100 and 85.71%, respectively. Angiography revealed contrast extravasation in 12 cases and a pseudoaneurysm in 3 cases. One patient developed a serious infection and died 2 days after the TAE. CONCLUSION: TAE with NBCA for PPH treatment following PD, especially for massive hemorrhage caused by a pancreatic fistula, biliary fistula, or inflammatory corrosion, can result in rapid and effective hemostasis with high safety.

Role of TRAK1 variants in epilepsy: genotype-phenotype analysis in a pediatric case of epilepsy with developmental disorder.

Purpose: The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. The aim of this study was to investigate the genotype-phenotype of TRAK1-associated epilepsy. Methods: Trio-based whole-exome sequencing was performed on a cohort of 98 patients with epilepsy of unknown etiologies. Protein modeling and the VarCards database were used to predict the damaging effects of the variants. Detailed neurological phenotypes of all patients with epilepsy having TRAK1 variants were analyzed to assess the genotype-phenotype correlations. Results: A novel TRAK1 compound heterozygous variant comprising variant c.835C > T, p.Arg279Cys and variant c.2560A > C, p.Lys854Gln was identified in one pediatric patient. Protein modeling and VarCards database analyses revealed that the variants were damaging. The patient received a diagnosis of early infantile epileptic spasms with a developmental disorder; he became seizure-free through valproate and adrenocorticotropic hormone treatment. Further results for six variants in 12 patients with epilepsy indicated that biallelic TRAK1 variants (including homozygous or compound heterozygous variants) were associated with epilepsy with developmental disorders. Among these patients, eight (67%) had epileptic spasms and seven (58%) were intractable to anti-seizure medicines. Moreover, eight patients experienced refractory status epilepticus, of which seven (88%) died in early life. To our knowledge, this is the first reported case of epilepsy caused by TRAK1 compound heterozygous variants. Conclusion: Biallelic TRAK1 variants can cause epilepsy and developmental disorders. In these patients, seizures progress to status epilepticus, suggesting a high risk for poor outcomes and the requirement of early treatment.

Aging in the dermis: Fibroblast senescence and its significance.

Skin aging is characterized by changes in its structural, cellular, and molecular components in both the epidermis and dermis. Dermal aging is distinguished by reduced dermal thickness, increased wrinkles, and a sagging appearance. Due to intrinsic or extrinsic factors, accumulation of excessive reactive oxygen species (ROS) triggers a series of aging events, including imbalanced extracellular matrix (ECM) homeostasis, accumulation of senescent fibroblasts, loss of cell identity, and chronic inflammation mediated by senescence-associated secretory phenotype (SASP). These events are regulated by signaling pathways, such as nuclear factor erythroid 2-related factor 2 (Nrf2), mechanistic target of rapamycin (mTOR), transforming growth factor beta (TGF-ß), and insulin-like growth factor 1 (IGF-1). Senescent fibroblasts can induce and accelerate age-related dysfunction of other skin cells and may even cause systemic inflammation. In this review, we summarize the role of dermal fibroblasts in cutaneous aging and inflammation. Moreover, the underlying mechanisms by which dermal fibroblasts influence cutaneous aging and inflammation are also discussed.

Investigation of FRMPD4 variants associated with X-linked epilepsy.

BACKGROUND: The etiology of unexplained epilepsy in most patients remains unclear. Variants of FRMPD4 are suggested to be associated with neurodevelopmental disorders. Therefore, we screened for disease-causing FRMPD4 variants in patients with epilepsy. METHODS: Trios-based whole-exome sequencing was conducted on a cohort of 85 patients with unexplained epilepsy, their parents, and extended family members. Additional cases with FRMPD4 variants were identified from the China Epilepsy Gene Matching Platform V.1.0. The frequency of variants was analyzed, and their subregional effects were predicted using in silico tools. The genotype-phenotype correlation of the newly defined causative genes and protein stability were analyzed using I-Mutant V.3.0 and Grantham scores. RESULTS: Two novel missense variants of FRMPD4 were identified in two families. Using the gene matching platform, we identified three additional novel missense variants. These variants presented at low or no allele frequencies in the gnomAD database. All the variants were located outside the three FRMPD4 main domains (WW, PDZ, and FERM). In silico analyses revealed that the variants were damaging and were predicted to be the least stable. All patients eventually became seizure-free. Eight of the 21 patients with FRMPD4 variants had epilepsy, of which five (63%) had missense variants located outside the domains, two had deletions involving exon 2, and one had a frameshift variant located outside the domains. Patients with epilepsy caused by missense variants were often free of intellectual disabilities (4/5), whereas patients with epilepsy caused by truncated variants had intellectual disabilities and structural brain abnormalities (3/3). CONCLUSIONS: The FRMPD4 gene is potentially associated with epilepsy. The genotype-phenotype correlation of FRMPD4 variants indicated that differences in variant types and locations of FRMPD4 may explain their phenotypic variation.

Improvement in Cutaneous Conditions Can Benefit Some Health Conditions in the Elderly.

As we are aging, a number of cutaneous and extracutaneous disorders will be developed. Although the pathogenesis of these aging-associated disorders is not clear yet, abnormalities in the skin are linked to some aging-associated disorders at least to some extent. Inflammatory dermatoses such as psoriasis and atopic dermatitis predispose to the development of cardiovascular diseases, obesity and type 2 diabetes. In addition, both chronologically aged skin and individuals with some aging-associated systemic conditions display altered epidermal function, such as reduced stratum corneum hydration levels, which can provoke cutaneous inflammation. Because aged skin exhibits higher expression levels of inflammatory cytokines, which play a pathogenic role in a variety of aging-associated health condition, the association of the skin with some aging-associated disorders is likely mediated by inflammation. This postulation is supported by the evidence that improvement in either epidermal function or inflammatory dermatoses can mitigate some aging-associated disorders such as mild cognitive impairment and insulin sensitivity. This perspective discusses the association of the skin with aging-associated disorders and highlights the potential of improvement in cutaneous conditions in the management of some health conditions in the elderly.

Development and evaluation of polyacrylamide microspheres loaded with phloretin and tantalum for transcatheter arterial embolization.

Transcatheter arterial embolization is an effective treatment for liver cancer. However, the development of novel embolic agents remains a challenge. In this study, we evaluated polyacrylic acid microspheres loaded with phloretin and tantalum as potential embolic agents for liver cancer treatment. Microspheres were synthesised via emulsion polymerisation and characterised in terms of size, shape, and drug-loading efficiency. Nanosized tantalum powder (0 to 15%) was added to the microspheres as an X-ray blocking agent. The maximum drug-loading capacity of the microspheres was approximately 20 mg g-1. The phloretin-loaded microspheres showed a sustained drug release profile in vitro. The microspheres were also evaluated for their in vivo anticancer efficacy in a rabbit VX2 liver tumour model. In conclusion, polyacrylic acid microspheres loaded with phloretin and tantalum have great potential as novel embolic agents for transcatheter arterial embolization for liver cancer treatment.

Link between the skin and autism spectrum disorder.

Autism spectrum disorder (ASD) is a common neurological disorder. Although the etiologies of ASD have been widely speculated, evidence also supports the pathogenic role of cutaneous inflammation in autism. The prevalence of ASD is higher in individuals with inflammatory dermatoses than in those without inflammatory diseases. Anti-inflammation therapy alleviates symptoms of ASD. Recent studies suggest a link between epidermal dysfunction and ASD. In the murine model, mice with ASD display epidermal dysfunction, accompanied by increased expression levels of proinflammatory cytokines in both the skin and the brain. Children with ASD, which develops in their early lifetime, also exhibit altered epidermal function. Interestingly, improvement in epidermal function alleviates some symptoms of ASD. This line of evidence suggests a pathogenic role of cutaneous dysfunction in ASD. Either an improvement in epidermal function or effective treatment of inflammatory dermatoses can be an alternative approach to the management of ASD. We summarize here the current evidence of the association between the skin and ASD.

Body Mass Index z Scores Correlate with Epidermal Function in Chinese Children.

Background/Objective: Epidermal function is altered in a number of cutaneous and extracutaneous disorders. To determine whether epidermal function is also altered in children with obesity, we assessed the correlation between the body mass index (BMI) z score and epidermal function in children. Participants and Methods: Participants were enrolled from outpatient clinic, schools and kindergartens. Epidermal biophysical properties, including transepidermal water loss rate, stratum corneum hydration and skin surface pH, were measured on the flexor forearm and shin. Correlations between epidermal biophysical properties and BMI were analyzed. In addition, the association of epidermal biophysical properties with BMI z score was also determined. Results: Overall, BMI did not differ significantly between boys and girls among the age groups. BMI z scores correlated negatively with stratum corneum hydration levels and positively with skin surface pH in boys, but not in girls. The negative correlation between TEWL and BMI z score was not significant. Moreover, stratum corneum hydration levels were lower in boys with a BMI z score of ≥2 than in those with a BMI z score of -2 to 0.99. Conclusion: Both stratum corneum hydration levels and skin surface pH are significantly correlated with BMI z scores in boys, but not in girls. Whether epidermal function influences BMI or vice versa remains to be determined.

Dynamic Changes in the Microbial Community and Metabolite Profile during the Pile Fermentation Process of Fuzhuan Brick Tea.

The pile fermentation process of Fuzhuan brick tea is unique in that it involves preheating without the use of starter cultures. The detailed metabolite changes and their drivers during this procedure are not known. Characterizing these unknown changes that occur in the metabolites and microbes during pile fermentation of Fuzhuan brick tea is important for industrial modernization of this traditional fermented food. Using microbial DNA amplicon sequencing, mass spectrometry-based untargeted metabolomics, and feature-based molecular networking, we herein reveal that significant changes in the microbial community occur before changes in the metabolite profile. These changes were characterized by a decrease in Klebsiella and Aspergillus, alongside an increase in Bacillus and Eurotium. The decrease in lysophosphatidylcholines, unsaturated fatty acids, and some astringent flavan-3-ols and bitter amino acids, as well as the increase in some less astringent flavan-3-ols and sweet or umami amino acids, contributed importantly to the overall changes observed in the metabolite profile. The majority of these changes was caused by bacterial metabolism and the corresponding heat generated by it.

Characterization and Differentiation of Grain Proteomes from Wild-Type Puroindoline and Variants in Wheat.

Premium wheat with a high end-use quality is generally lacking in China, especially high-quality hard and soft wheat. Pina-D1 and Pinb-D1 (puroindoline genes) influence wheat grain hardness (i.e., important wheat quality-related parameter) and are among the main targets in wheat breeding programs. However, the mechanism by which puroindoline genes control grain hardness remains unclear. In this study, three hard wheat puroindoline variants (MY26, GX3, and ZM1) were compared with a soft wheat variety (CM605) containing the wild-type puroindoline genotype. Specifically, proteomic methods were used to screen for differentially abundant proteins (DAPs). In total, 6253 proteins were identified and quantified via a high-throughput tandem mass tag quantitative proteomic analysis. Of the 208 DAPs, 115, 116, and 99 proteins were differentially expressed between MY26, GX3, and ZM1 (hard wheat varieties) and CM605, respectively. The cluster analysis of protein relative abundances divided the proteins into six clusters. Of these proteins, 67 and 41 proteins were, respectively, more and less abundant in CM605 than in MY26, GX3, and ZM1. Enrichment analyses detected six GO terms, five KEGG pathways, and five IPR terms that were shared by all three comparisons. Furthermore, 12 proteins associated with these terms or pathways were found to be differentially expressed in each comparison. These proteins, which included cysteine proteinase inhibitors, invertases, low-molecular-weight glutenin subunits, and alpha amylase inhibitors, may be involved in the regulation of grain hardness. The candidate genes identified in this study may be relevant for future analyses of the regulatory mechanism underlying grain hardness.

Association of Epidermal Biophysical Properties with Obesity and Its Implications.

BACKGROUND: Obesity is a condition defined by an excess amount of body fat, with body mass index (BMI) of 30 and higher. It is associated with a number of other medical conditions, including insulin resistance, diabetes mellitus, and cardiovascular diseases, as well as dyslipidemia, and it is also associated with several cutaneous disorders such as atopic dermatitis, psoriasis, intertriginous dermatitis, acanthosis nigricans and skin infections. SUMMARY: Evidence suggests a link between obesity and epidermal dysfunction. Generally, individuals with obesity display higher transepidermal water loss rate and lower stratum corneum hydration levels, although no association of obesity with epidermal dysfunction has been documented. Results of skin surface pH are controversial. But study demonstrated a positive correlation of BMI with skin surface pH on both the forearm and the shin in males, suggesting that the changes in epidermal function vary with gender in individuals with obesity. KEY MESSAGES: This review summarizes the association between obesity and epidermal function, and discusses possible underlying mechanisms. Individuals with obesity exhibit poor epidermal permeability barrier and lower stratum corneum hydration levels. Because of the pathogenic role of compromised epidermal function in inflammation, which is also linked to obesity, improvement in epidermal function could benefit individuals with obesity, particularly those with abnormalities in epidermal function.

Rosacea and seborrheic dermatitis differentially respond to lactic acid sting and capsaicin tests in Chinese women.

BACKGROUND: Although rosacea and seborrheic dermatitis share some symptoms of sensitive skin, whether they respond differently to lactic acid sting and capsaicin tests, common tests for diagnosis of sensitive skin, is unknown. OBJECTIVES: To reveal the cutaneous responses to lactic acid sting (LAST) and capsaicin test (CAT) in females with either rosacea vs. seborrheic dermatitis. METHODS: A total of 60 patients with rosacea, 20 patients with seborrheic dermatitis and 40 normal controls were enrolled in the study. Their skin sensitivity to stimuli were evaluated following topical application of either 10% lactic acid solution or 0.001% capsaicin solution. Transepidermal water loss (TEWL) rates and erythema indexes were also measured on the face. RESULTS: In comparison to normal controls, the positive rate to either LAST or CAT was significantly higher in subjects with rosacea (p < 0.001), but not in that with seborrheic dermatitis. Similarly, individuals with rosacea displayed a higher positive rate to both LAST and CAT than those with seborrheic dermatitis and normal controls (p < 0.001). In parallel, the LAST scores and CAT scores in individuals with rosacea were significantly higher than in that with either seborrheic dermatitis or normal controls (p < 0.001). The baseline TEWL rates and erythema indexes were higher in individual with rosacea than in normal controls (p < 0.001). But the baseline TEWL rates and erythema indexes did not differ significantly between subjects with rosacea and that with seborrheic dermatitis. Moreover, LAST scores and CAT scores correlated positively with TEWL (p < 0.0001). TEWL rates were higher in CAT positive than in CAT negative subjects (p < 0.0001). Finally, erythema index correlated positively with CAT scores (p < 0.0001), but not with LAST scores (p = 0.0842). CONCLUSIONS: Skin responses to LAST and CAT differ between individuals with rosacea and those with seborrheic dermatitis, possibly due to the differences in epidermal permeability barrier and the neurovascular hyperreactivity. The higher LAST and CAT scores, as well as positive rates of both LAST and CAT can be attributable to inferior permeability barrier and the neurovascular hyperreactivity in subjects with rosacea.

Psoriasis and COVID-19 Infection Negatively Impact Each Other: An Analysis of 3581 Cases.

Objective: To determine whether COVID-19 infection and psoriasis impact each other. Methods: WeChat app was used to carry out a questionnaire survey in individuals aged 18 years and over. Results: A total of 3581 individuals, including 2515 individuals without psoriasis and 1066 psoriatic patients completed the survey. The rate of COVID-19 infection was significantly higher in psoriatic patients than in those without psoriasis (89.59% vs 77.93%, p < 0.0001). Moreover, the rate of relapse and/or worsening of psoriasis was higher in psoriatic patients with COVID-19 infection than in that without COVID-19 infection (75.29% vs 47.75%, p < 0.0001). Conclusion: COVID-19 infection and psoriasis negatively impact each other.